Ro 28-2653 | CAS#261956-22-3 | MMP inhibitor

MedKoo Cat#: 563157 | Name: Ro 28-2653

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ro 28-2653 is an inhibitor of matrix-metalloproteinases (MMPs) with high selectivity for MMP2, MMP9 and membrane type 1-MMP. Ro 28-2653 reproducibly reduced the tumor weights by up to 90% in a dose-dependent manner. In addition, an inhibitory effect in rats with established tumors (treatment start at day 6) was shown. A significantly prolonged survival of Ro 28-2653-treated rats was also demonstrated.

Chemical Structure

Ro 28-2653

CAS#261956-22-3

Theoretical Analysis

MedKoo Cat#: 563157

Name: Ro 28-2653

CAS#: 261956-22-3

Chemical Formula: C26H23N5O5

Exact Mass: 485.1699

Molecular Weight: 485.50

Elemental Analysis: C, 64.32; H, 4.78; N, 14.43; O, 16.48

Price and Availability

Size	Price	Availability
5mg	USD 270.00	2 Weeks
10mg	USD 445.00	2 Weeks
25mg	USD 775.00	2 Weeks
50mg	USD 1,150.00	2 Weeks
100mg	USD 1,850.00	2 Weeks

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Synonym

Ro 28-2653; Ro 28 2653; Ro 282653; Ro-28-2653; Ro282653;

IUPAC/Chemical Name

5-([1,1'-biphenyl]-4-yl)-5-(4-(4-nitrophenyl)piperazin-1-yl)pyrimidine-2,4,6(1H,3H,5H)-trione

InChi Key

NJKTYSXXGARILV-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H23N5O5/c32-23-26(24(33)28-25(34)27-23,20-8-6-19(7-9-20)18-4-2-1-3-5-18)30-16-14-29(15-17-30)21-10-12-22(13-11-21)31(35)36/h1-13H,14-17H2,(H2,27,28,32,33,34)

SMILES Code

O=C1NC(C(C2=CC=C(C3=CC=CC=C3)C=C2)(N4CCN(C5=CC=C([N+]([O-])=O)C=C5)CC4)C(N1)=O)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.03.00

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

RO 28-2653 is a potent, selective and orally active matrix-metalloproteinases (MMPs) MMP2, MMP9 and MMP14 inhibitor with IC50 of 10, 12 and 10 nM, shows no activity against MMP3 and MMP1 (IC50>1 uM). RO 28-2653 reduces the growth of tumors induced by the inoculation of different cell lines producing MMPs and inhibits the tumor-promoting effect of fibroblasts on breast adenocarcinoma cells. RO 28-2653 reduces tumor growth and prolongs survival in a prostate cancer standard rat model.

In vitro activity:

High concentrations of RO-28-2653 impair mitochondrial function, although there is less impairment compared to amytal and 2,4-DNP. Reference: Biochem Pharmacol. 2002 Feb 15;63(4):725-32. https://pubmed.ncbi.nlm.nih.gov/11992641/

In vivo activity:

In an acute stroke model involving rats, Ro 28-2653 significantly reduced brain injury only when administered in the first 2 days after focal cerebral ischemia. Reference: Brain Res. 2011 Jan 12;1368:264-70. https://pubmed.ncbi.nlm.nih.gov/20971083/

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	20.60

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 485.50 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Opalka JR, Gellerich FN, Kling L, Müller-Beckmann B, Zierz S. Effect of the new matrix metalloproteinase inhibitor RO-28-2653 on mitochondrial function. Biochem Pharmacol. 2002 Feb 15;63(4):725-32. doi: 10.1016/s0006-2952(01)00867-x. PMID: 11992641. 2. Nagel S, Heinemann PV, Heiland S, Koziol J, Gardner H, Wagner S. Selective MMP-inhibition with Ro 28-2653 in acute experimental stroke--a magnetic resonance imaging efficacy study. Brain Res. 2011 Jan 12;1368:264-70. doi: 10.1016/j.brainres.2010.10.057. Epub 2010 Oct 21. PMID: 20971083. 3. Kilian M, Gregor JI, Heukamp I, Hanel M, Ahlgrimm M, Schimke I, Kristiansen G, Ommer A, Walz MK, Jacobi CA, Wenger FA. Matrix metalloproteinase inhibitor RO 28-2653 decreases liver metastasis by reduction of MMP-2 and MMP-9 concentration in BOP-induced ductal pancreatic cancer in Syrian Hamsters: inhibition of matrix metalloproteinases in pancreatic cancer. Prostaglandins Leukot Essent Fatty Acids. 2006 Dec;75(6):429-34. doi: 10.1016/j.plefa.2006.08.004. Epub 2006 Oct 10. PMID: 17034997.

In vitro protocol:

In vivo protocol:

1. Nagel S, Heinemann PV, Heiland S, Koziol J, Gardner H, Wagner S. Selective MMP-inhibition with Ro 28-2653 in acute experimental stroke--a magnetic resonance imaging efficacy study. Brain Res. 2011 Jan 12;1368:264-70. doi: 10.1016/j.brainres.2010.10.057. Epub 2010 Oct 21. PMID: 20971083. 2. Kilian M, Gregor JI, Heukamp I, Hanel M, Ahlgrimm M, Schimke I, Kristiansen G, Ommer A, Walz MK, Jacobi CA, Wenger FA. Matrix metalloproteinase inhibitor RO 28-2653 decreases liver metastasis by reduction of MMP-2 and MMP-9 concentration in BOP-induced ductal pancreatic cancer in Syrian Hamsters: inhibition of matrix metalloproteinases in pancreatic cancer. Prostaglandins Leukot Essent Fatty Acids. 2006 Dec;75(6):429-34. doi: 10.1016/j.plefa.2006.08.004. Epub 2006 Oct 10. PMID: 17034997.

1: Lee AJ, Feng E, Chew MV, Balint E, Poznanski SM, Giles E, Zhang A, Marzok A, Revill SD, Vahedi F, Dubey A, Ayaub E, Jimenez-Saiz R, McGrath JJC, Ritchie TM, Jordana M, Jonigk DD, Ackermann M, Ask K, Miller M, Richards CD, Ashkar AA. Type I interferon regulates proteolysis by macrophages to prevent immunopathology following viral infection. PLoS Pathog. 2022 May 5;18(5):e1010471. doi: 10.1371/journal.ppat.1010471. PMID: 35512020; PMCID: PMC9113601. 2: Belgiovine C, Chiesa G, Chiodi I, Frapolli R, Bonezzi K, Taraboletti G, D'Incalci M, Mondello C. Snail levels control the migration mechanism of mesenchymal tumor cells. Oncol Lett. 2016 Jul;12(1):767-771. doi: 10.3892/ol.2016.4642. Epub 2016 May 30. PMID: 27347214; PMCID: PMC4907273. 3: Yin Z, Sada AA, Reslan OM, Narula N, Khalil RA. Increased MMPs expression and decreased contraction in the rat myometrium during pregnancy and in response to prolonged stretch and sex hormones. Am J Physiol Endocrinol Metab. 2012 Jul 1;303(1):E55-70. doi: 10.1152/ajpendo.00553.2011. Epub 2012 Apr 10. PMID: 22496348; PMCID: PMC3404560. 4: Galvani S, Trayssac M, Augé N, Thiers JC, Calise D, Krell HW, Sallusto F, Kamar N, Rostaing L, Thomsen M, Nègre-Salvayre A, Salvayre R. A key role for matrix metalloproteinases and neutral sphingomyelinase-2 in transplant vasculopathy triggered by anti-HLA antibody. Circulation. 2011 Dec 13;124(24):2725-34. doi: 10.1161/CIRCULATIONAHA.111.021790. Epub 2011 Nov 14. PMID: 22082680. 5: Belgiovine C, Frapolli R, Bonezzi K, Chiodi I, Favero F, Mello-Grand M, Dei Tos AP, Giulotto E, Taraboletti G, D'Incalci M, Mondello C. Reduced expression of the ROCK inhibitor Rnd3 is associated with increased invasiveness and metastatic potential in mesenchymal tumor cells. PLoS One. 2010 Nov 30;5(11):e14154. doi: 10.1371/journal.pone.0014154. PMID: 21209796; PMCID: PMC3014295. 6: Nagel S, Heinemann PV, Heiland S, Koziol J, Gardner H, Wagner S. Selective MMP-inhibition with Ro 28-2653 in acute experimental stroke--a magnetic resonance imaging efficacy study. Brain Res. 2011 Jan 12;1368:264-70. doi: 10.1016/j.brainres.2010.10.057. Epub 2010 Oct 21. PMID: 20971083. 7: Woenne EC, Lederle W, Zwick S, Palmowski M, Krell H, Semmler W, Mueller MM, Kiessling F. MMP inhibition blocks fibroblast-dependent skin cancer invasion, reduces vascularization and alters VEGF-A and PDGF-BB expression. Anticancer Res. 2010 Mar;30(3):703-11. PMID: 20392987. 8: Breyholz HJ, Wagner S, Faust A, Riemann B, Höltke C, Hermann S, Schober O, Schäfers M, Kopka K. Radiofluorinated pyrimidine-2,4,6-triones as molecular probes for noninvasive MMP-targeted imaging. ChemMedChem. 2010 May 3;5(5):777-89. doi: 10.1002/cmdc.201000013. PMID: 20373323. 9: Muñoz M, Heimesaat MM, Danker K, Struck D, Lohmann U, Plickert R, Bereswill S, Fischer A, Dunay IR, Wolk K, Loddenkemper C, Krell HW, Libert C, Lund LR, Frey O, Hölscher C, Iwakura Y, Ghilardi N, Ouyang W, Kamradt T, Sabat R, Liesenfeld O. Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. J Exp Med. 2009 Dec 21;206(13):3047-59. doi: 10.1084/jem.20090900. Epub 2009 Dec 7. PMID: 19995958; PMCID: PMC2806449. 10: Raffetto JD, Barros YV, Wells AK, Khalil RA. MMP-2 induced vein relaxation via inhibition of [Ca2+]e-dependent mechanisms of venous smooth muscle contraction. Role of RGD peptides. J Surg Res. 2010 Apr;159(2):755-64. doi: 10.1016/j.jss.2008.09.022. Epub 2008 Oct 24. PMID: 19482300; PMCID: PMC2844458. 11: Raffetto JD, Khalil RA. Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol. 2008 Jan 15;75(2):346-59. doi: 10.1016/j.bcp.2007.07.004. Epub 2007 Jul 7. PMID: 17678629; PMCID: PMC2254136. 12: Kilian M, Gregor JI, Heukamp I, Hanel M, Ahlgrimm M, Schimke I, Kristiansen G, Ommer A, Walz MK, Jacobi CA, Wenger FA. Matrix metalloproteinase inhibitor RO 28-2653 decreases liver metastasis by reduction of MMP-2 and MMP-9 concentration in BOP-induced ductal pancreatic cancer in Syrian Hamsters: inhibition of matrix metalloproteinases in pancreatic cancer. Prostaglandins Leukot Essent Fatty Acids. 2006 Dec;75(6):429-34. doi: 10.1016/j.plefa.2006.08.004. Epub 2006 Oct 10. PMID: 17034997. 13: Ludolph AC. Matrix metalloproteinases--a conceptional alternative for disease-modifying strategies in ALS/MND? Exp Neurol. 2006 Oct;201(2):277-80. doi: 10.1016/j.expneurol.2006.05.013. Epub 2006 Jun 30. PMID: 16808915. 14: Abramjuk C, Lein M, Rothaug W, Krell HW, Loening SA, Jung K. Enhanced inhibitory effect of the matrix metalloproteinase inhibitor Ro 28-2653 in combination with estramustine and etoposide on the prostate carcinoma in the rat Dunning orthotopic tumor model. Cancer Chemother Pharmacol. 2007 Feb;59(2):275-82. doi: 10.1007/s00280-006-0269-7. Epub 2006 Jun 7. PMID: 16758188. 15: Piette M, Evrard B, Frankenne F, Chiap P, Bertholet P, Castagne D, Foidart JM, Delattre L, Piel G. Pharmacokinetic study of a new synthetic MMP inhibitor (Ro 28-2653) after IV and oral administration of cyclodextrin solutions. Eur J Pharm Sci. 2006 Jun;28(3):189-95. doi: 10.1016/j.ejps.2006.01.011. Epub 2006 Mar 6. PMID: 16520026. 16: Lorenzl S, Narr S, Angele B, Krell HW, Gregorio J, Kiaei M, Pfister HW, Beal MF. The matrix metalloproteinases inhibitor Ro 28-2653 [correction of Ro 26-2853] extends survival in transgenic ALS mice. Exp Neurol. 2006 Jul;200(1):166-71. doi: 10.1016/j.expneurol.2006.01.026. Epub 2006 Mar 3. PMID: 16516196. 17: Genter MB, Warner BM, Krell HW, Bolon B. Reduction of alachlor-induced olfactory mucosal neoplasms by the matrix metalloproteinase inhibitor Ro 28-2653. Toxicol Pathol. 2005;33(5):593-9. doi: 10.1080/01926230500244522. PMID: 16178123. 18: Ye YN, Wu WK, Shin VY, Cho CH. A mechanistic study of colon cancer growth promoted by cigarette smoke extract. Eur J Pharmacol. 2005 Sep 5;519(1-2):52-7. doi: 10.1016/j.ejphar.2005.07.009. PMID: 16125168. 19: Bertholet P, Gueders M, Dive G, Albert A, Barillaro V, Perly B, Cataldo D, Piel G, Delattre L, Evrard B. The effect of cyclodextrins on the aqueous solubility of a new MMP inhibitor: phase solubility, 1 H-NMR spectroscopy and molecular modeling studies, preparation and stability study of nebulizable solutions. J Pharm Pharm Sci. 2005 Jul 14;8(2):163-74. PMID: 16124927. 20: Abramjuk C, Jung K, Krell HW, Juchem R, Peters R, Taymoorian K, Staack A, Stephan C, Schnorr J, Loening SA, Lein M. Matrix metalloproteinase inhibitor Ro 28-2653 in combination with estramustine: tumor-reducing effects on hormone- sensitive prostate cancer in rats. Anticancer Drugs. 2005 Sep;16(8):855-61. doi: 10.1097/01.cad.0000173477.05358.ec. PMID: 16096433.